KMT5C_RAT
ID KMT5C_RAT Reviewed; 470 AA.
AC P0C2N6;
DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 1.
DT 03-AUG-2022, entry version 99.
DE RecName: Full=Histone-lysine N-methyltransferase KMT5C {ECO:0000305};
DE EC=2.1.1.362 {ECO:0000250|UniProtKB:Q86Y97};
DE AltName: Full=Lysine-specific methyltransferase 5C {ECO:0000312|RGD:1305226};
DE AltName: Full=Suppressor of variegation 4-20 homolog 2;
DE Short=Su(var)4-20 homolog 2;
DE Short=Suv4-20h2;
DE AltName: Full=[histone H4]-N-methyl-L-lysine20 N-methyltransferase KMT5B {ECO:0000305};
DE EC=2.1.1.362 {ECO:0000250|UniProtKB:Q86Y97};
DE AltName: Full=[histone H4]-lysine20 N-methyltransferase KMT5B {ECO:0000305};
DE EC=2.1.1.361 {ECO:0000250|UniProtKB:Q86Y97};
GN Name=Kmt5c {ECO:0000312|RGD:1305226}; Synonyms=Suv420h2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Soares M.B., Casavant T.L., Sheffield V.C., Bonaldo M.F., Bair T.B.,
RA Scheetz T.E., Snir E., Akabogu I., Bair J.L., Berger B., Crouch K.,
RA Davis A., Eystone M.E., Keppel C., Kucaba T.A., Lebeck M., Lin J.L.,
RA de Melo A.I.R., Rehmann J., Reiter R.S., Schaefer K., Smith C., Tack D.,
RA Trout K., Lin J.J.-C.;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP INDUCTION.
RX PubMed=17182829; DOI=10.1093/jn/137.1.216s;
RA Pogribny I.P., Tryndyak V.P., Muskhelishvili L., Rusyn I., Ross S.A.;
RT "Methyl deficiency, alterations in global histone modifications, and
RT carcinogenesis.";
RL J. Nutr. 137:216S-222S(2007).
RN [3]
RP INDUCTION.
RX PubMed=16497704; DOI=10.1093/carcin/bgi364;
RA Pogribny I.P., Ross S.A., Tryndyak V.P., Pogribna M., Poirier L.A.,
RA Karpinets T.V.;
RT "Histone H3 lysine 9 and H4 lysine 20 trimethylation and the expression of
RT Suv4-20h2 and Suv-39h1 histone methyltransferases in hepatocarcinogenesis
RT induced by methyl deficiency in rats.";
RL Carcinogenesis 27:1180-1186(2006).
CC -!- FUNCTION: Histone methyltransferase that specifically methylates
CC monomethylated 'Lys-20' (H4K20me1) and dimethylated 'Lys-20' (H4K20me2)
CC of histone H4 to produce respectively dimethylated 'Lys-20' (H4K20me2)
CC and trimethylated 'Lys-20' (H4K20me3) and thus regulates transcription
CC and maintenance of genome integrity. In vitro also methylates
CC unmodified 'Lys-20' (H4K20me0) of histone H4 and nucleosomes (By
CC similarity). H4 'Lys-20' trimethylation represents a specific tag for
CC epigenetic transcriptional repression. Mainly functions in pericentric
CC heterochromatin regions, thereby playing a central role in the
CC establishment of constitutive heterochromatin in these regions. KMT5C
CC is targeted to histone H3 via its interaction with RB1 family proteins
CC (RB1, RBL1 and RBL2) (By similarity). Facilitates TP53BP1 foci
CC formation upon DNA damage and proficient non-homologous end-joining
CC (NHEJ)-directed DNA repair by catalyzing the di- and trimethylation of
CC 'Lys-20' of histone H4 (By similarity). May play a role in class switch
CC reconbination by catalyzing the di- and trimethylation of 'Lys-20' of
CC histone H4 (By similarity). {ECO:0000250|UniProtKB:Q6Q783,
CC ECO:0000250|UniProtKB:Q86Y97}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine
CC = H(+) + N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60348, Rhea:RHEA-COMP:15555, Rhea:RHEA-
CC COMP:15556, ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:61929, ChEBI:CHEBI:61976; EC=2.1.1.362;
CC Evidence={ECO:0000250|UniProtKB:Q86Y97};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:60349;
CC Evidence={ECO:0000250|UniProtKB:Q86Y97};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N(6),N(6)-dimethyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-
CC methionine = H(+) + N(6),N(6),N(6)-trimethyl-L-lysyl(20)-[histone H4]
CC + S-adenosyl-L-homocysteine; Xref=Rhea:RHEA:61992, Rhea:RHEA-
CC COMP:15556, Rhea:RHEA-COMP:15998, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57856, ChEBI:CHEBI:59789, ChEBI:CHEBI:61961,
CC ChEBI:CHEBI:61976; Evidence={ECO:0000250|UniProtKB:Q86Y97};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61993;
CC Evidence={ECO:0000250|UniProtKB:Q86Y97};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(20)-[histone H4] + S-adenosyl-L-methionine = H(+) +
CC N(6)-methyl-L-lysyl(20)-[histone H4] + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:60344, Rhea:RHEA-COMP:15554, Rhea:RHEA-COMP:15555,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.361;
CC Evidence={ECO:0000250|UniProtKB:Q86Y97};
CC -!- ACTIVITY REGULATION: Inhibited by 6,7-Dichloro-N-cyclopentyl-4-
CC (pyridin-4-yl)phthalazin-1-amine (A-196).
CC {ECO:0000250|UniProtKB:Q86Y97}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with HP1 proteins CBX1,
CC CBX3 and CBX5. Interacts with RB1 family proteins RB1, RBL1 and RBL2
CC (By similarity). {ECO:0000250|UniProtKB:Q6Q783}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Associated with
CC pericentric heterochromatin. CBX1 and CBX5 are required for the
CC localization to pericentric heterochromatin.
CC -!- INDUCTION: Strongly down-regulated in various cancers such as
CC hepatocarcinomas. {ECO:0000269|PubMed:16497704,
CC ECO:0000269|PubMed:17182829}.
CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase
CC superfamily. Histone-lysine methyltransferase family. Suvar4-20
CC subfamily. {ECO:0000255|PROSITE-ProRule:PRU00903}.
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DR EMBL; AY724526; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001100945.1; NM_001107475.1.
DR RefSeq; XP_006228321.1; XM_006228259.1.
DR RefSeq; XP_006228322.1; XM_006228260.1.
DR RefSeq; XP_006228323.1; XM_006228261.1.
DR RefSeq; XP_006228325.1; XM_006228263.1.
DR RefSeq; XP_006228326.1; XM_006228264.1.
DR RefSeq; XP_006228327.1; XM_006228265.3.
DR RefSeq; XP_006228328.1; XM_006228266.1.
DR AlphaFoldDB; P0C2N6; -.
DR SMR; P0C2N6; -.
DR STRING; 10116.ENSRNOP00000023744; -.
DR iPTMnet; P0C2N6; -.
DR PhosphoSitePlus; P0C2N6; -.
DR PaxDb; P0C2N6; -.
DR Ensembl; ENSRNOT00000023744; ENSRNOP00000023744; ENSRNOG00000017508.
DR GeneID; 308345; -.
DR KEGG; rno:308345; -.
DR UCSC; RGD:1305226; rat.
DR CTD; 84787; -.
DR RGD; 1305226; Kmt5c.
DR eggNOG; KOG2589; Eukaryota.
DR GeneTree; ENSGT00940000161700; -.
DR HOGENOM; CLU_040002_0_0_1; -.
DR InParanoid; P0C2N6; -.
DR OMA; GGWTAHY; -.
DR OrthoDB; 236983at2759; -.
DR PhylomeDB; P0C2N6; -.
DR TreeFam; TF106433; -.
DR Reactome; R-RNO-3214841; PKMTs methylate histone lysines.
DR PRO; PR:P0C2N6; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000017508; Expressed in ovary and 20 other tissues.
DR Genevisible; P0C2N6; RN.
DR GO; GO:0000779; C:condensed chromosome, centromeric region; ISO:RGD.
DR GO; GO:0000792; C:heterochromatin; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005721; C:pericentric heterochromatin; ISO:RGD.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISO:RGD.
DR GO; GO:0042799; F:histone methyltransferase activity (H4-K20 specific); ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:1904047; F:S-adenosyl-L-methionine binding; ISS:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; ISS:UniProtKB.
DR GO; GO:0034772; P:histone H4-K20 dimethylation; IEA:InterPro.
DR GO; GO:0034773; P:histone H4-K20 trimethylation; ISO:RGD.
DR GO; GO:0016571; P:histone methylation; ISO:RGD.
DR GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; ISS:UniProtKB.
DR GO; GO:0045830; P:positive regulation of isotype switching; ISS:UniProtKB.
DR CDD; cd19185; SET_KMT5C; 1.
DR Gene3D; 1.10.10.1700; -; 1.
DR Gene3D; 2.170.270.10; -; 1.
DR InterPro; IPR041938; Hist-Lys_N-MTase_N.
DR InterPro; IPR044425; KMT5C_SET.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR039977; Suv4-20/Set9.
DR InterPro; IPR025790; Suv4-20_animal.
DR PANTHER; PTHR12977; PTHR12977; 1.
DR Pfam; PF00856; SET; 1.
DR SMART; SM00317; SET; 1.
DR SUPFAM; SSF82199; SSF82199; 1.
DR PROSITE; PS51570; SAM_MT43_SUVAR420_2; 1.
DR PROSITE; PS50280; SET; 1.
PE 2: Evidence at transcript level;
KW Chromatin regulator; Chromosome; Metal-binding; Methyltransferase; Nucleus;
KW Reference proteome; Repressor; S-adenosyl-L-methionine; Transcription;
KW Transcription regulation; Transferase; Zinc.
FT CHAIN 1..470
FT /note="Histone-lysine N-methyltransferase KMT5C"
FT /id="PRO_0000281795"
FT DOMAIN 104..218
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT REGION 350..443
FT /note="Required for heterochromatin localization"
FT /evidence="ECO:0000250"
FT BINDING 32
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86Y97"
FT BINDING 114..117
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86Y97"
FT BINDING 121
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86Y97"
FT BINDING 160
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86Y97"
FT BINDING 169
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86Y97"
FT BINDING 182..183
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86Y97"
FT BINDING 185
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q86Y97"
FT BINDING 229
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q86Y97"
FT BINDING 230
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q86Y97"
FT BINDING 231
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q86Y97"
FT BINDING 234
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q86Y97"
SQ SEQUENCE 470 AA; 53607 MW; 060148E2FFFB49AB CRC64;
MGPDRVTARE LCENDDLATS LVLDPYLGFR THKMNVSPVP TLRRQHHLRS ALEAFLRQRD
LEAAFRALTL GGWMAHYFQN RAPRQEAALK NHIFCYLRAF LPESGFTILP CTRYSMETNG
AKIVSTRAWK KNEKLELLVG CIAELREEDE YLLRAGENDF SVMYSTRKRS AQLWLGPAAF
INHDCKPNCK FVPSDGNTAC VKVLRDIEPG DEVTCFYGEG FFGEKNEHCE CYTCERKGEG
AFRLQPREPE LRPRPLDKYE LRETKRRLQQ CLDSSQQNLL SLRACSHLSP LRPDPFCAAC
QPSCLLPVSP HMDYLPLWLQ WVPQPQPRVR PRKRRRRRRR RPRIPQASLS PDLHTACVSL
HRWGGCGPHC QLRAEAMVTL HLLPQTRWTP KQDWYWARRY GLPSVVRVEL SPLAPALPAA
PAPAGNLGPT PTPDLIPKQA LAFAPFCPPK RLRLVVSHGS IDLDINSGEP
